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Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.
This presentation will enable the learner to:
1.Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis
2.Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management
The course of illness in obsessive–compulsive disorder (OCD) varies significantly between patients. Little is known about factors predicting a chronic course of illness. The aim of this study is to identify factors involved in inducing and in maintaining chronicity in OCD.
The present study is embedded within the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study, an ongoing multicenter naturalistic cohort study designed to identify predictors of long-term course and outcome in OCD. For this study, 270 subjects with a current diagnosis of OCD were included. Chronicity status at 2-year follow-up was regressed on a selection of baseline predictors related to OCD, to comorbidity and to stress and support.
Psychotrauma [odds ratio (OR) 1.98, confidence interval (CI) 1.22–3.22, p = 0.006], recent negative life events (OR 1.42, CI 1.01–2.01, p = 0.043), and presence of a partner (OR 0.28, CI 0.09–0.85, p = 0.025) influenced the risk of becoming chronic. Longer illness duration (OR 1.46, CI 1.08–1.96, p = 0.013) and higher illness severity (OR 1.09, CI 1.03–1.16, p = 0.003) increased the risk of remaining chronic.
External influences increase the risk of becoming chronic, whereas the factors involved in maintaining chronicity are illness-related. As the latter are potentially difficult to modify, treatment should be devoted to prevent chronicity from occurring in the first place. Therapeutic strategies aimed at alleviating stress and at boosting social support might aid in achieving this goal.
Marbling is an economically important factor in many beef carcass grading schemes. This study aimed to evaluate marbling traits of longissimus thoracis muscle (LT) with different methods: USDA marbling score, intramuscular fat (IMF) content by image analysis of X-ray computed tomography (CT) scans and by conventional analytical method. Bulls (n=46) were slaughtered at an average weight of 536 kg and an average age of 646 days. Mean values of EUROP fat scores varied from 2− to 2+, whereas mean values of EUROP conformation grade from O0 to R0. Average growth rate of bulls was 955 g/day. Average chemical fat content of LT varied from 2.2% to 3.1% across conformation classes, and from 2.3% to 5.0% across fat classes. Intramuscular fat content in the 12th rib and in LT on CT-scans closely correlated with chemical fat content (r=0.81 and 0.85, respectively). The highest frequency of USDA marbling score was ‘small’ (55.2%), followed by ‘slight’ (25.5%), ‘modest’ (17%) and ‘moderate’ (2.1%). Computed tomography scans of LT can be used for the evaluation of marbling in Hungarian Simmental cattle. Bulls with higher growth rate had lower marbling level in LT (r=−0.4 to −0.5). EUROP conformation and fat scores have no relationship with marbling traits in this specific cattle population.
Intramuscular connective tissue plays an important role in meat tenderness. Our objective was to compare the collagen/hydroxyproline content and X-ray computed tomographic (CT) connective tissue proportion of longissimus thoracis (LT) muscle in Hungarian Simmental bulls and cows. Cows had lower carcass weight (247 kg v. 295 kg), EU conformation score (3.5 v. 5.5) and fatness score (4.2 v. 5.9) than bulls (P<0.01). Bulls had higher LT area, but intramuscular fat content was similar for bulls and cows. On the other hand, bulls had lower CT intramuscular connective tissue proportion in LT compared with cows (0.41±0.21% v. 0.66±0.28%, P<0.01). The same tendency could be observed for the collagen content (0.50±0.21% v. 0.67±0.11%, P<0.01). Correlation between the CT connective tissue proportion of LT and collagen content was r=0.8. There was a weak positive correlation between slaughter age and CT connective tissue as well as collagen content of LT (r=0.3 to 0.4). In conclusion, intramuscular connective tissue proportion in LT increased with slaughter age and older cows had higher collagen and connective tissue proportion than bulls. Mixed CT scans can be used for the analysis of intramuscular connective tissue content.
Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).
In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression.
Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure.
We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.
Data-constrained modeling is a method that enables three-dimensional distribution of mineral phases and porosity in a sample to be modeled based on micro-computed tomography scans acquired at different X-ray energies. Here we describe an alternative method for measuring porosity, synchrotron K-edge subtraction using xenon gas as a contrast agent. Results from both methods applied to the same Darai limestone sample are compared. Reasonable agreement between the two methods and with other porosity measurements is obtained. The possibility of a combination of data-constrained modeling and K-edge subtraction methods for more accurate sample characterization is discussed.
To test the hypothesis that cognitive impairment in older adults is associated with all-cause mortality risk and the risk increases when the degree of cognitive impairment augments; and then, if this association is confirmed, to report the population-attributable fraction (PAF) of mortality due to cognitive impairment.
A representative random community sample of individuals aged over 55 was interviewed, and 4557 subjects remaining alive at the end of the first year of follow-up were included in the analysis. Instruments used in the assessment included the Mini-Mental Status Examination (MMSE), the History and Aetiology Schedule (HAS) and the Geriatric Mental State (GMS)-AGECAT. For the standardised degree of cognitive impairment Perneczky et al's MMSE criteria were applied. Mortality information was obtained from the official population registry. Multivariate Cox proportional hazard models were used to test the association between MMSE degrees of cognitive impairment and mortality risk. We also estimated the PAF of mortality due to specific MMSE stages.
Cognitive impairment was associated with mortality risk, the risk increasing in parallel with the degree of cognitive impairment (Hazard ratio, HR: 1.18 in the ‘mild’ degree of impairment; HR: 1.29 in the ‘moderate’ degree; and HR: 2.08 in the ‘severe’ degree). The PAF of mortality due to severe cognitive impairment was 3.49%.
A gradient of increased mortality-risk associated with severity of cognitive impairment was observed. The results support the claim that routine assessment of cognitive function in older adults should be considered in clinical practice.
Metabolomics is the comprehensive study of metabolites, which are the substrates, intermediate, and end products of cellular metabolism. The heritability of the concentrations of circulating metabolites bears relevance for evaluating their suitability as biomarkers for disease. We report aspects of familial resemblance for the concentrations in human serum of more than 100 metabolites, measured using a targeted metabolomics platform. Age- and sex-corrected monozygotic twin correlations, midparent–offspring regression coefficients, and spouse correlations in subjects from two independent cohorts (Netherlands Twin Register and Leiden Longevity Study) were estimated for each metabolite. In the Netherlands Twin Register subjects, who were largely fasting, we found significant monozygotic twin correlations for 121 out of 123 metabolites. Heritability was confirmed by midparent–offspring regression. For most detected metabolites, the correlations between spouses were considerably lower than those between twins, indicating a contribution of genetic effects to familial resemblance. Remarkably high heritability was observed for free carnitine (monozygotic twin correlation 0.66), for the amino acids serine (monozygotic twin correlation 0.77) and threonine (monozygotic twin correlation 0.64), and for phosphatidylcholine acyl-alkyl C40:3 (monozygotic twin correlation 0.77). For octenoylcarnitine, a consistent point estimate of approximately 0.50 was found for the spouse correlations in the two cohorts as well as for the monozygotic twin correlation, suggesting that familiality for this metabolite is explained by shared environment. We conclude that for the majority of metabolites targeted by the used metabolomics platform, the familial resemblance of serum concentrations is largely genetic. Our results contribute to the knowledge of the heritability of fasting serum metabolite concentrations, which is relevant for biomarker research.
Thus far collaborative stepped care (CSC) studies have not incorporated self-help as a first step.
To evaluate the effectiveness of CSC in the treatment of common mental disorders.
An 8-month cluster randomised controlled trial comparing CSC to care as usual (CAU) (Dutch Trial Register identifier NTR1224). The CSC consisted of a stepped care approach guided by a psychiatric nurse in primary care with the addition of antidepressants dependent on the severity of the disorder, followed by cognitive–behavioural therapy in mental healthcare.
Twenty general practitioners (GPs) and 8 psychiatric nurses were randomised to provide CSC or CAU. The GPs recruited 163 patients of whom 85% completed the post-test measurements. At 4-month mid-test CSC was superior to CAU: 74.7% (n = 68) v. 50.8% (n = 31) responders (P = 0.003). At 8-month post-test and 12-month follow-up no significant differences were found as the patients in the CAU group improved as well.
Treatment within a CSC model resulted in an earlier treatment response compared with CAU.
The hen's egg, in the form of table eggs and egg products, forms a staple part of the world's total protein consumption. In the last century, there has been considerable research effort focusing on ways of improving egg production and enhancing the quality of eggs. More recently, and with the development and application of new molecular technologies, our understanding and knowledge of how an egg is formed, what it actually consists of, in terms of its major versus minor components, and what the functional roles of each of these components might be, have been greatly enhanced. For example, new previously unknown molecules with specific activity or functional properties have been discovered in the egg albumen and yolk, some of which have potential uses in pharmaceutical and other food related applications. This review paper, which is the collaborative effort of members of Working Group 4 - Quality of Eggs and Egg Products - of the European Federation of WPSA, describes the scientific research behind a number of these major advances and provides some insight to the focus of current research in this area.
We study optical processes relevant to optical amplification and lasing in CdSe nanocrystal quantum dots (NQD). NQDs are freestanding nanoparticles prepared using solution-based organometallic reactions originally developed for the Cd chalcogenides, CdS, CdSe and CdTe [J. Am. Chem. Soc. 115, 8706 (1993)]. We investigate NQDs with diameters ranging from 2 to 8 nm. Due to strong quantum confinement, they exhibit size-dependent spectral tunability over an energy range as wide as several hundred meV. We observe a strong effect of the matrix/solvent on optical gain properties of CdSe NQDs. In most of the commonly used solvents (such as hexane and toluene), gain is suppressed due to strong photoinduced absorption associated with carriers trapped at solvent-related interface states. In contrast, matrix-free close packed NQD films (NQD solids) exhibit large optical gain with a magnitude that is sufficiently high for the optical gain to successfully compete with multiparticle Auger recombination [Science 287, 10117 (2000)]. These films exhibit narrowband stimulated emission at both cryogenic and room temperature, and the emission color is tunable with dot size [Science 290, 314 (2000)]. Moreover, the NQD films can be incorporated into microcavities of different geometries (micro-spheres, wires, tubes) that produce lasing in whispering gallery modes. The facile preparation, chemical flexibility and wide-range spectral tunability due to strong quantum confinement are the key advantages that should motivate research into NQD applications in optical amplifiers and lasers.
Understanding the nature of specific neural activity is essential to the progression of research in the field of brain disorders and diseases, as well as neuroprosthetics. Microelectrodes are the primary measurement devices used to transduce neural activity into electrical signals to help neuroscientists study dynamic brain function. Advances in signal processing and packaging currently allow neural recording for periods as long as a year by use of chronically implanted electrodes in freely behaving animals. Stability of the electrode impedance is required for optimum signal recording over the length of the recording interval. While electrode–tissue interaction plays a major role in the quality of the recorded signal, delamination or degradation of the dielectric coating also interferes with signal recording. Therefore, to improve the signal recording process, it is useful to understand how the electrode design and component materials affect the signal over the course of time.
Thin films of lead-titanate were deposited by chemical vapor deposition (CVD) using tetraethyl lead and titanium isopropoxide. Good high frequency hysteresis curves were obtained with platinum contacts. Low resistance of the material (estimated at 108 ohm-cm) affected low frequency measurements.
Optimized experimental parameters (pressure, temperature, gas flows, oxidizer) were derived from a designed experimental matrix using response surface methodology. This approach significantly reduced the number of deposition trials required.
A series of two-phase chromium silicide base intermetallics have been investigated with respect to creep behavior and oxidation resistance. The first results of these investigations are reported. Good oxidation resistance has been demonstrated in one composition, which was due to the formation of the protective vitrious SiO2 layer, while the chromium oxide layer is very helpful at the intermediate temperature range.
The quasibinary NiAI-Mo system exhibits a large two-phase field between NiAl and the terminal (Mo) solid solution, and offers the potential for producing in-situ eutectic composites for high-temperature structural applications. The phase stability of this composite system was experimentally evaluated, following long-term exposures at elevated temperatures. Bend strengths as a function of temperature and room-temperature fracture toughness data are presented for selected NiA1-Mo alloys, together with results from fractography observations.